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Residual diseases after conization of women with stage IA–IB1 cervical carcinoma in region with high incidence
Abstracts / Gynecologic Oncology 133 (2014) 2–207
(2.38), and bone and joints (2.70). The risk of secondary cancer at esophagus, anus, and bone and joints did not increase in subgroup with the interval less than 60 months. Interestingly, the decreasing overall SIR for a secondary cancer was breast (0.82) for all follow up period and rectum (0.66) for follow up period up to 59 months. This might be explained by ovarian ablation from treatment for cervical cancer and the shared radiotherapy field. Conclusions: The secondary cancer was significantly identified in women after treatment of cervical cancer rather than in the general population. The incidence of breast and rectal cancer decreased after treatment of cervical cancer. doi:10.1016/j.ygyno.2014.03.483
464 — Poster Session B STAT1 pathway promotes progression of serous papillary endometrial cancer T. Baba, B. Kharma, N. Matsumura, K. Yamaguchi, J. Hamanishi, K. Abiko, I. Konishi. Kyoto University, Kyoto, Japan. Objectives: Serous papillary endometrial cancers (SPEC) are highly progressive with poor prognosis, and its oncogenic profile is known different from endometrioid endometrial cancers. It, however, still remains unclear that which pathway promotes tumor progression. In this study, we aimed to figure out SPEC-specific pathways through genome-wide analysis to reveal the mechanism promoting tumor growth and progression. Methods: Gene expression microarray and immunohistochemical staining were conducted using 69 samples of endometrial cancer under protocols approved by the Institutional Review Board to investigate SPEC-specific pathways. Using SPAC-1L, a SPEC cell line, cellular proliferation, migration, and invasion were assessed with or without siRNAs for target genes. In vivo tumorigenesis was also assessed with NOD-SCID mice. Results: Gene expression microarray analysis revealed STAT1 pathway was highly activated in SPECs, and STAT1 expression was confirmed significantly higher in SPECs by immunohistochemical staining (P b 0.001). Immunohistochemical staining also exhibited co-localization of ICAM-1 and PD-L1 at tumor frontier with prominent infiltration of CD8-T cells in SPECs (P b 0.001). IFN-g induced gene expression of cMyc, ICAM-1 and PD-L1 (P b 0.05) as well as STAT1 in SPAC-1L cells, and promoted cellular proliferation (P b 0.05), adhesion (P b 0.0001), and invasion (P = 0.0002). In contrast, suppression of STAT1 attenuated induction of these genes (P b 0.05), and inhibited invasion (P b 0.05) and xenograft tumor growth on NOD-SCID mice (P b 0.0001). Conclusions: These results indicate that STAT1 pathway is specifically activated in SPECs to be associated with their aggressive features. Concerning immune-activity at tumor microenvironment, targeting STAT1 pathway with attenuation of tumor-immunity could be a potent candidate in the treatment of SPECs although further analysis is mandatory. doi:10.1016/j.ygyno.2014.03.484
465 — Poster Session B Residual diseases after conization of women with stage IA–IB1 cervical carcinoma in region with high incidence U. Chatchotikawong, I. Ruengkhachorn. Gynecologic Oncology Division, Bangkoknoi, Thailand. Objectives: To determine rate of residual diseases, influencing factors after conization, and survival outcome of women with stage IA to IB1 cervical carcinoma in region with high incidence.
183
Methods: A retrospective study of 185 stage IA to IB1 cervical carcinoma patients who had undergone cervical conization followed by hysterectomy during 2006–2012. Patients' characteristics, histopathologic data and survival data were recorded. Independent factors correlated with residual lesions in the subsequent hysterectomy specimens were analyzed by descriptive statistics. Regression analysis was used for determined predicting factors for residual cancer. Survival function was analyzed by Kaplan–Meier method. Results: The mean age of studied patients was 48.89 (range 25–78) years old. 74 women (40%) were menopause. The most common symptom is check-up, 141 patients (76.2%). The most abnormal cervical cytology was HSIL, 86 women (54.1%), the second was SCCA, 35 women (22%). Cone specimen was free margin in 28 women (15.9%). In case of having diseases at margin, we found SIL to be 32.7% and cancer to be 53.2%. The most common histologic type were SCCA (129 women, 69.7%), and adenocarcinoma (40 women, 21.6%). Pathology of hysterectomy specimens found residual cancer in 70 women (37.8%), CIN in 42 women (22.7%). 184 patients (99.5%) were complete response. 6 women had disease recurrence and 5 patients were cured after treatment for recurrent diseases. One patient was alive with disease progression. Postmenopause, having diseases and type of diseases at conization margins, depth of invasion of cone specimens and FIGO stage were significantly correlated with residual cancer in hysterectomy specimens. The mean progression free survival was 84.25 months (95% CI 80.76–87.75). Conclusions: Pathologic margin, depth of invasion in cone tissue, and postmenopause were independent risk factors for residual cancer in stage IA to IB1 cervical carcinoma after conization. doi:10.1016/j.ygyno.2014.03.485
466 — Poster Session B A metabolomic approach to identifying platinum resistance in ovarian cancer R.R. Rattan, L. Poisson, I. Datta, C. Tebbe, S. Dar, S.H. Alford, T.E. Buekers, S. Giri, A.R. Munkarah. Henry Ford Health System, Detroit, MI, USA. Objectives: The “Warburg Effect” refers to the differences in metabolism between cancer and normal cells. Acquisition of metabolic alterations has been shown to be essential for the unremitting growth of cancer; the relation of such alterations to chemo-sensitivity has not been investigated. The objective of this study is to identify the metabolic alterations that are specifically associated with platinum resistance, using a global metabolomic approach in two epithelial ovarian cancer cell lines. Methods: A global metabolic analysis of the A2780 platinumsensitive and its isogeneic platinum-resistant C200 ovarian cancer cell line was performed utilizing ultra-high performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy. Per-metabolite comparisons were made between cell lines and an interpretive analysis was carried out using the KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic library and the Ingenuity exogenous molecule library. Results: Of the 253 identified metabolites, 152 were found to be dissimilar (P b 0.05) between A2780 and C200 cells. Of these, 57 had increased and 92 had decreased levels in C200. The top altered KEGG pathways based on significant difference or impact of alterations were: 1) cysteine and methionine; 2) d-arginine and ornithine; 3) starch and sucrose; 4) amino sugar and nucleotide; 5) pyrimidine and 6) glutathione pathways. The glutathione pathway has been implicated to play a key role in platinum resistance in ovarian cancer as well as other malignancies. An ingenuity pathway analysis revealed networks of altered metabolites related to free radical scavenging, drug metabolism, and molecular transport. This novel finding can be explained by the known mechanism of action of cisplatin, and suggests that adaptations
(2.38), and bone and joints (2.70). The risk of secondary cancer at esophagus, anus, and bone and joints did not increase in subgroup with the interval less than 60 months. Interestingly, the decreasing overall SIR for a secondary cancer was breast (0.82) for all follow up period and rectum (0.66) for follow up period up to 59 months. This might be explained by ovarian ablation from treatment for cervical cancer and the shared radiotherapy field. Conclusions: The secondary cancer was significantly identified in women after treatment of cervical cancer rather than in the general population. The incidence of breast and rectal cancer decreased after treatment of cervical cancer. doi:10.1016/j.ygyno.2014.03.483
464 — Poster Session B STAT1 pathway promotes progression of serous papillary endometrial cancer T. Baba, B. Kharma, N. Matsumura, K. Yamaguchi, J. Hamanishi, K. Abiko, I. Konishi. Kyoto University, Kyoto, Japan. Objectives: Serous papillary endometrial cancers (SPEC) are highly progressive with poor prognosis, and its oncogenic profile is known different from endometrioid endometrial cancers. It, however, still remains unclear that which pathway promotes tumor progression. In this study, we aimed to figure out SPEC-specific pathways through genome-wide analysis to reveal the mechanism promoting tumor growth and progression. Methods: Gene expression microarray and immunohistochemical staining were conducted using 69 samples of endometrial cancer under protocols approved by the Institutional Review Board to investigate SPEC-specific pathways. Using SPAC-1L, a SPEC cell line, cellular proliferation, migration, and invasion were assessed with or without siRNAs for target genes. In vivo tumorigenesis was also assessed with NOD-SCID mice. Results: Gene expression microarray analysis revealed STAT1 pathway was highly activated in SPECs, and STAT1 expression was confirmed significantly higher in SPECs by immunohistochemical staining (P b 0.001). Immunohistochemical staining also exhibited co-localization of ICAM-1 and PD-L1 at tumor frontier with prominent infiltration of CD8-T cells in SPECs (P b 0.001). IFN-g induced gene expression of cMyc, ICAM-1 and PD-L1 (P b 0.05) as well as STAT1 in SPAC-1L cells, and promoted cellular proliferation (P b 0.05), adhesion (P b 0.0001), and invasion (P = 0.0002). In contrast, suppression of STAT1 attenuated induction of these genes (P b 0.05), and inhibited invasion (P b 0.05) and xenograft tumor growth on NOD-SCID mice (P b 0.0001). Conclusions: These results indicate that STAT1 pathway is specifically activated in SPECs to be associated with their aggressive features. Concerning immune-activity at tumor microenvironment, targeting STAT1 pathway with attenuation of tumor-immunity could be a potent candidate in the treatment of SPECs although further analysis is mandatory. doi:10.1016/j.ygyno.2014.03.484
465 — Poster Session B Residual diseases after conization of women with stage IA–IB1 cervical carcinoma in region with high incidence U. Chatchotikawong, I. Ruengkhachorn. Gynecologic Oncology Division, Bangkoknoi, Thailand. Objectives: To determine rate of residual diseases, influencing factors after conization, and survival outcome of women with stage IA to IB1 cervical carcinoma in region with high incidence.
183
Methods: A retrospective study of 185 stage IA to IB1 cervical carcinoma patients who had undergone cervical conization followed by hysterectomy during 2006–2012. Patients' characteristics, histopathologic data and survival data were recorded. Independent factors correlated with residual lesions in the subsequent hysterectomy specimens were analyzed by descriptive statistics. Regression analysis was used for determined predicting factors for residual cancer. Survival function was analyzed by Kaplan–Meier method. Results: The mean age of studied patients was 48.89 (range 25–78) years old. 74 women (40%) were menopause. The most common symptom is check-up, 141 patients (76.2%). The most abnormal cervical cytology was HSIL, 86 women (54.1%), the second was SCCA, 35 women (22%). Cone specimen was free margin in 28 women (15.9%). In case of having diseases at margin, we found SIL to be 32.7% and cancer to be 53.2%. The most common histologic type were SCCA (129 women, 69.7%), and adenocarcinoma (40 women, 21.6%). Pathology of hysterectomy specimens found residual cancer in 70 women (37.8%), CIN in 42 women (22.7%). 184 patients (99.5%) were complete response. 6 women had disease recurrence and 5 patients were cured after treatment for recurrent diseases. One patient was alive with disease progression. Postmenopause, having diseases and type of diseases at conization margins, depth of invasion of cone specimens and FIGO stage were significantly correlated with residual cancer in hysterectomy specimens. The mean progression free survival was 84.25 months (95% CI 80.76–87.75). Conclusions: Pathologic margin, depth of invasion in cone tissue, and postmenopause were independent risk factors for residual cancer in stage IA to IB1 cervical carcinoma after conization. doi:10.1016/j.ygyno.2014.03.485
466 — Poster Session B A metabolomic approach to identifying platinum resistance in ovarian cancer R.R. Rattan, L. Poisson, I. Datta, C. Tebbe, S. Dar, S.H. Alford, T.E. Buekers, S. Giri, A.R. Munkarah. Henry Ford Health System, Detroit, MI, USA. Objectives: The “Warburg Effect” refers to the differences in metabolism between cancer and normal cells. Acquisition of metabolic alterations has been shown to be essential for the unremitting growth of cancer; the relation of such alterations to chemo-sensitivity has not been investigated. The objective of this study is to identify the metabolic alterations that are specifically associated with platinum resistance, using a global metabolomic approach in two epithelial ovarian cancer cell lines. Methods: A global metabolic analysis of the A2780 platinumsensitive and its isogeneic platinum-resistant C200 ovarian cancer cell line was performed utilizing ultra-high performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy. Per-metabolite comparisons were made between cell lines and an interpretive analysis was carried out using the KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic library and the Ingenuity exogenous molecule library. Results: Of the 253 identified metabolites, 152 were found to be dissimilar (P b 0.05) between A2780 and C200 cells. Of these, 57 had increased and 92 had decreased levels in C200. The top altered KEGG pathways based on significant difference or impact of alterations were: 1) cysteine and methionine; 2) d-arginine and ornithine; 3) starch and sucrose; 4) amino sugar and nucleotide; 5) pyrimidine and 6) glutathione pathways. The glutathione pathway has been implicated to play a key role in platinum resistance in ovarian cancer as well as other malignancies. An ingenuity pathway analysis revealed networks of altered metabolites related to free radical scavenging, drug metabolism, and molecular transport. This novel finding can be explained by the known mechanism of action of cisplatin, and suggests that adaptations